Potent chemopreventive agents against pancreatic cancer

Development of pancreatic cancers is clinically so silent in general that at the time of diagnosis, the vast majority of cases are incurable with a very poor prognosis. Therefore, effective preventive approaches against this aggressive disease are urgently required. Experimentally, carcinogenesis process is assumed to consist of at least two stages named initiation and promotion. Using a two-stage model of hamster pancreatic carcinogenesis, we have reported stage-specific inhibitory effects by a number of potent cancer chemopreventive agents. Among them, phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables, remarkably blocked the initiation phase of pancreatic as well as lung carcinogenesis in hamsters initiated with N-nitrosobis(2-oxopropyl)amine (BOP). However, PEITC failed to affect both pancreatic and lung carcinogenesis when given during the post-initiation (promotion) phase of carcinogenesis. In contrast, our recent study clearly demonstrated that a cyclooxygenase (COX)-2 inhibitor substantially protects against BOP-induced pancreatic tumors in hamsters in line with decrease in cell proliferative activity of pancreatic ducts when given in the post-initiation phase. Interestingly, trypsin inhibitors inhibited both initiation and post-initiation phases of BOP-induced pancreatic carcinogenesis although they are known to induce hyperplastic acinar lesions in the rat pancreas. Taken together with these data, our review is aimed at looking over mechanistic insights into potent chemopreventive agents against pancreatic cancer.